The invention relates to the object that is characterized in the claims, i.e., a device for magnetic separation of pharmaceutical preparations, their starting or intermediate products that contain a separation space, in which a magnetic gradient field prevails and which has an inlet and an outlet, process for separating magnetic materials from pharmaceutical preparations, and agents that are produced with the aid of the device according to the invention and the process according to the invention.
In pharmaceutical preparations, foreign particles in the form of metallic particulate contaminants can result from production operations with metal tools or in metal containers or by injection instruments. For the protection of patients, therefore, the pharmacopeia stipulate the maximum limits, weighted according to particle size, for the number of foreign particles for pharmaceutical preparations that are to be administered parenterally, here especially in the case of infusions. These foreign particles are frequently ferromagnetic, ferrimagnetic, superparamagnetic or paramagnetic compounds.
Naturally occurring ferromagnetic contaminants of a starting substance can be separated according to a process that is described in U.S. Pat. No. 4,119,700. Here, the ferromagnetic contaminants are separated with the aid of a magnetic field. Processes for magnetic separation of biological materials are known from laid-open specifications WO 90/07380 and WO 83/02405. Laid-open specification WO 90/07380 describes a device in which a separation space is surrounded by a permanent magnet and which has an inlet and an outlet.
In the case of pharmaceutical preparations, the number of foreign particles to date is reduced if at all possible by processes of adsorption filtration or membrane filtration. Especially in the case of contaminants that are produced by user actions, such as, e.g., spraying pharmaceutical agents into infusion containers, however, it is difficult to reduce the number of foreign particles since correspondingly small-pore membrane filters often can be operated only with additional mechanical pressure. In most cases, filter inserts in infusion instruments therefore have pore sizes of several micrometers, which, however, lead to unsatisfactory retention rates for foreign particles. In the case of particulate pharmaceutical preparations, such as, e.g., parenteral fat emulsions or crystal suspensions as depot dosage forms, separating foreign particles by membrane or adsorption filtration is generally not possible at all.
The object of this invention was therefore to develop a device that makes it possible to separate magnetic particles, such as, e.g., metal contaminants, quickly and simply from pharmaceutical preparations and to simplify the separation process to such an extent that it can be done by the user himself.
This object is achieved by this invention.
A device for magnetic separation of pharmaceutical preparations, their starting or intermediate products that contain a separation space, in which a magnetic gradient field prevails and which has an inlet and an outlet, was developed that is characterized by the following feature: the device is designed in the form of an attachment filter for injection instruments or infusion instruments.
The device makes it possible to separate all compounds that are ferromagnetic, ferrimagnetic, superparamagnetic, or paramagnetic.
The gradient field that is used for separation has to be considerably stronger than the gradient of the natural field. The selection of the suitable gradient field depends on the magnetic moment of the substance that is to be separated. To separate paramagnetic compounds from diamagnetic pharmaceutical preparations, high-gradient fields are necessary.
To separate the undesirable magnetic compounds, the respective pharmaceutical preparation or its starting or intermediate product is directed through the device and thus through a magnetic gradient field. The higher the gradient of the magnetic gradient field, the stronger the force that acts on the paramagnetic, ferrimagnetic, superparamagnetic, or ferromagnetic contaminants. Pharmaceutical agents and pharmaceutical adjuvants (such as, for example, water) are generally diamagnetic and therefore experience a force that is very low in comparison to the paramagnetic, ferrimagnetic, superparamagnetic, or ferromagnetic contaminants; moreover, said force does not cause them to travel in the direction of the gradient but rather repels them. To separate magnetic contaminants from diamagnetic preparations, therefore, in contrast to filtration through small-pore filters (e.g., 0.22 xcexcm membrane filter), no special pressure generally needs to be exerted in the separation according to the invention in the magnetic gradient field; generally the force of gravity or hydrostatic pressure is sufficient.
With the device according to the invention, the separation of the undesirable magnetic particles is carried out with the aid of a flow process. In the case of flow processes, in contrast to static processes, the flow rate has to be matched to the magnetic moments of the ferromagnetic, ferrimagnetic, or superparamagnetic substances that are to be separated and the field gradients that are applied.
The embodiment of the device according to the invention can be implemented in different ways. The magnetic gradient field in the separation space can be generated by, for example, a permanent magnet or an electromagnet that is attached outside the separation space. To increase the locally effective gradient of the magnetic field, it can be very helpful in this case for the separation space to consist of paramagnetic or soft-magnetic material and/or to contain paramagnetic or preferably soft-magnetic material.
The magnetic gradient field in the separation space can, however, also be generated by a permanent-magnetic material which forms the separation space or is found in a separation space.
In addition, the magnetic gradient field in the separation space can be generated by a conductor through which the current flows and which is located either in the separation space or surrounds the separation space. In both the above-mentioned cases, it can again be very helpful for the separation space to consist of paramagnetic or soft-magnetic material and/or to contain paramagnetic or preferably soft-magnetic material.
Soft-magnetic substances are preferably soft-magnetic iron or steel, especially in the form of fine shot (e.g., balls a few millimeters in diameter) or frits or in the form of wire (such as, e.g., steel wool, nets, or sieves).
The walls of the separation space, as well as the soft-magnetic or paramagnetic materials and the conductors through which the current flows and that are found within the separation space can also be provided with suitable protective layers for protection against undesirable chemical reactions, such as, e.g., corrosion. Such protective layers can be the materials that are known from materials science. Suitable are, for example, chromium platings, protective layers made of stable oxides (such as aluminum oxide), or plastic coatings (e.g., PVC, polystyrene, polyethylene). When conductors through which current flows are used inside the separation chamber to generate the magnetic gradient fields, insulation with known insulating materials (such as, e.g., plastics in the form of paint coatings) is necessary in any case.